Shen et al. BMC Geriatrics (2017) 17:188 DOI 10.1186/s12877-017-0569-2
RESEARCH ARTICLE
Open Access
The impact of frailty and sarcopenia on postoperative outcomes in older patients undergoing gastrectomy surgery: a systematic review and meta-analysis Yanjiao Shen1,2,3†, Qiukui Hao1,3†, Jianghua Zhou3 and Birong Dong1,3*
Abstract Background: Gastric cancer is a major health problem, and frailty and sarcopenia will affect the postoperative outcomes in older people. However, there is still no systematic review to determine the role of frailty and sarcopenia in predicting postoperative outcomes among older patients with gastric cancer who undergo gastrectomy surgery. Methods: We searched Embase, Medline through the Ovid interface and PubMed websites to identify potential studies. All the search strategies were run on August 24, 2016. We searched the Google website for unpublished studies on June 1, 2017. The data related to the endpoints of gastrectomy surgery were extracted. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the association between sarcopenia and adverse postoperative outcomes by using Stata version 11.0. PRISMA guidelines for systematic reviews were followed. Results: After screening 500 records, we identified eight studies, including three prospective cohort studies and five retrospective cohort studies. Only one study described frailty, and the remaining seven studies described sarcopenia. Frailty was statistically significant for predicting hospital mortality (OR 3.96; 95% CI: 1.12–14.09, P = 0.03). Sarcopenia was also associated with postoperative outcomes (pooled OR 3.12; 95% CI: 2.23–4.37). No significant heterogeneity was observed across these pooled studies (Chi2 = 3.10, I2 = 0%, P = 0.685). Conclusion: Sarcopenia and frailty seem to have significant adverse impacts on the occurrence of postoperative outcomes. Well-designed prospective cohort studies focusing on frailty and quality of life with a sufficient sample are needed. Keywords: Gastric cancer, Sarcopenia, Frailty, Postoperative complications
Background Gastric cancer constitutes a major health problem worldwide and is the second most common cause of cancer death [1]. Surgical resection is the main treatment for gastric cancer. Several studies have pointed out that old and young patients carry potential differences in surgery [2, 3]. Older gastric-cancer patients who undergo gastrointestinal surgery may encounter more adverse * Correspondence: [email protected] † Equal contributors 1 The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, #37 Guoxuexiang, Chengdu, Sichuan 610041, China 3 Collaborative Innovation Center of Sichuan for Elderly Care and Health, No. 783, Xindu Lu, Chengdu, Sichuan 610500, China Full list of author information is available at the end of the article
postoperative outcomes than younger patients [4]. Thus, the need exists to assess the risk of gastrointestinal surgery, especially in older gastric cancer patients. The prevalence of frailty increases with aging [5]. Frailty is defined as a clinically recognisable state of older adults with increased vulnerability, resulting from age-associated decline in physiological reserve and function across multiple organ systems [5, 6]. Frailty assessment may be a very useful tool for preoperative risk assessment in gastric cancer patients. By assessing frailty, patients can be assigned to undergo either a more tailored individual approach or a standard treatment [5]. Sarcopenia is a syndrome characterised by progressive and generalised loss of skeletal muscle mass and
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Shen et al. BMC Geriatrics (2017) 17:188
strength [7] and is an important geriatric syndrome closely related to frailty syndrome [8–10]. Increasing evidence shows that frailty or sarcopenia is related to the risk of adverse postoperative outcomes, including morbidity, institutionalisation, prolonged length of hospitalisation, and mortality [2, 9, 11]. Therefore, assessment of frailty and sarcopenia is necessary for older gastric-cancer patients potentially undergoing surgery [5, 12–14]. However, studies concerning the benefit of assessing frailty and sarcopenia in older patients with gastric cancer undergoing gastric surgery are scarce, and the conclusions are inconsistent [2, 9, 11, 15]. Therefore, we conducted this systematic review and meta-analysis aiming to examine the impact of frailty or sarcopenia on postoperative outcomes in older patients undergoing elective gastrectomy surgery.
Methods Search strategy
We searched the following electronic databases: (1) MEDLINE (Ovid, 1946 to August 24, 2016); (2) EMBASE (Ovid, 1974 to August 24, 2016). We used medical subject headings (MeSH) or equivalent and text word terms for MEDLINE and adaptations of the search strategy for EMBASE. We also searched the PubMed web version on August 24, 2016 (https://www.ncbi.nlm.nih.gov/ pubmed/), and Google website (www.google.com) for unpublished studies on June 1, 2017. As mentioned in the methodology specified under the PRISMA guidelines (www.prisma-statement.org), two researchers (YJS and JHZ), in collaboration with a medical librarian, performed a systematic search. The following keywords were used for the search: gastric cancer, aged, frailty, sarcopenia, geriatric assessment, postoperative complications and postoperative outcomes. The search string is included in detail in the Additional file 1. We tailored searches to individual databases. The search was completed on August 24, 2016, and animal restriction was applied. In addition, the reference lists of the selected articles were also reviewed to identify relevant articles. Study selection
Studies were eligible if they reported postoperative outcomes in older patients with gastric cancer in relation to frailty or sarcopenia profile. We included both retrospective and prospective cohort studies, which described clinical trials in which patients, with an average age of 60 years and older, underwent elective gastric surgery for gastric cancer and were categorised into frail or sarcopenic and non-frail or non-sarcopenic groups. In addition, the criteria used to categorise the patients into frail or sarcopenic groups had to be clearly reported, and frailty or sarcopenia had to be determined in a clinical setting. Studies were excluded if they did not examine postoperative
Page 2 of 8
outcomes or surgical complications such as wound infection, anastomotic leakage or mortality as endpoints. The titles and abstracts of the articles were screened by two investigators (YJS and JHZ). Whenever an article was considered relevant, we reviewed the full text. Finally, to identify potentially eligible studies, we also reviewed all the references in lists of the included studies. We resolved disagreements by discussion to reach a consensus with a third review author (BRD). Data charting
One reviewer (YJS) extracted the following data from the included studies: first author, study population, study design, sample size, age of the participants (mean age and standard deviation, if reported), year of publication, country and period of enrolment and inclusion and exclusion criteria of the study. Another reviewer (JHZ) independently double-checked this process. We extracted data regarding the targeted endpoints of this review: criteria and prevalence of frailty and sarcopenia and postoperative outcomes in relation to frailty and sarcopenia groups. If the data in the original manuscript was insufficient, the corresponding author was contacted for additional information. Critical appraisal
Reviewers YJS and JHZ independently assessed the methodological quality of the included studies by the Methodological Index for Non-Randomized Studies (MINORS). For non-comparative studies, this instrument consists of the following eight items: (1) a clearly stated aim, (2) inclusion of consecutive patients, (3) prospective collection of data, (4) endpoints appropriate to the aim of the study, (5) unbiased assessment of the study endpoint, (6) follow-up period appropriate to the aim of the study, (7) loss to follow-up less than 5% and (8) prospective calculation of the study size. If the information is not reported, an item is scored 0 points; if the information is reported but inadequate, it scores 1 point; if the information is reported and adequate, it scores 2 points. The ideal score is 16 for noncomparative studies. During a consensus meeting, disagreement among the reviewers was discussed with a third reviewer (BRD). Statistical analysis
If there was no available data to extract and pool, we described the outcomes in our review. The summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of the included studies were used as measures to assess the association of sarcopenia with postoperative complications. We measured heterogeneity by using the chi2 test with significance set at P < 0.1. The I2 is also computed; it is a quantitative measure of inconsistency
Shen et al. BMC Geriatrics (2017) 17:188
across studies. The following is a rough guide to interpretation of I2: 0% to 30% might not be important; 30% to 60% may represent moderate heterogeneity; 60% to 75% may represent substantial heterogeneity; 75% to 100% represents considerable heterogeneity. Clinically, there is heterogeneity because of the different evaluation methods of sarcopenia and follow-up time. In consideration of the presence of clinical heterogeneity, we used the random-effects model to synthesise all data, regardless of heterogeneity between the pooled studies in statistical order to obtain more conservative results. Publication bias was assessed by visually inspecting the funnel plots and Egger’s and Begg’s tests (P < 0.10). Subgroup analysis was conducted according to different designs of included studies. Sensitivity analysis was performed by omitting each study or included studies with lower quality. The STATA version 11.0 (Stata Corp, College Station, TX, USA) was used to perform all of the analyses. If a P value was 65
Japan
prospective study
7/2012–1/2015
Inclusion - Elective gastric surgery Exclusion - combined resection
ASA grade ≤ III gastric denocarcinoma
255
65.14 (10.81)
China
prospective study
8/2014–3/2015
Inclusion - Elective gastric surgery Exclusion - unresectable
Tegels JJ et al., 2015 [15]
gastric adenocarcinoma
149
69.6 (37–88)
Netherlands retrospective study
1/2005–9/2012
Inclusion - Elective gastric surgery Exclusion - None
Zhuang CL et al., 2016 [24]
gastric cancer
937
64.0 (median15.0)
China
retrospective study
12/2008–4/2013 Inclusion - Elective gastric surgery Exclusion - None
Chen FF et al., 2016 [19]
undergoing TG with 158 D2 lymphadenectomy for gastric cancer
66.9 ± 8.7
China
prospective study
8/2014–2/2016
Nishigori T et al., 2016 [25]
gastric cancer
>60 Japan (average age)
retrospective study
3/2006–10/2014 Inclusion –LTG Exclusion -None
157
Design
Inclusion - histologically proven gastric adenocarcinoma -ASA grade of III or less Exclusion - unresectable
Legend: SD standard deviation, NR not reported. LTG laparoscopic total gastrectomy, ECOG Eastern Cooperative Oncology Group
One study (Tegels, JJ et al.) [20] used GFI ≥3 to define frailty, and the results show a significant relationship between frailty and surgical mortality in gastric cancer (OR 3.96; 95% CI: 1.12 to 14.09, P = 0.03). This study also explored the relationship between frailty and serious adverse events, length of stay, and 6-month mortality. In this study, frailty was associated with increased risk of serious adverse events (defined as Clavien–Dindo grade 3a or over); however, frailty did not correlate with either increased 6-month mortality or increased length of stay. Six studies reported the association between sarcopenia and postoperative complications. We calculated the summary OR values using random-effects models; the pooled OR of gastric cancer from the combination of included studies was 3.12 (95% CI: 2.23–4.37) for
studies were hospitalised patients with a mean age over 60 years old, and the prevalence of sarcopenia ranged from 12.5% [23] to 57.7% [15]. Frailty or sarcopenia and postoperative outcomes
The outcomes reported in all included studies in relation to frailty or sarcopenia were in-hospital mortality [20], postoperative complications [19, 21–25], serious adverse events [20, 22, 24], hospital costs [23], overall survival [24], disease-free survival [24] and surgical site infection [25]. The postoperative complications of the studies were classified into different severity grades by using a well-described classification system (Clavien–Dindo, 2004) [26]. The classification systems used are summarised in Table 4. Table 2 Results of the MINORS quality assessment Study, Author, year
Clearly stated aim
Inclusion of consecutive patients
Consecutive patients Prospective collection of data
Endpoints appropriate to the aim of the study
Unbiased assessment of the study endpoint
Follow-up period appropriate to the aim of the study
Loss to follow-up
RESEARCH ARTICLE
Open Access
The impact of frailty and sarcopenia on postoperative outcomes in older patients undergoing gastrectomy surgery: a systematic review and meta-analysis Yanjiao Shen1,2,3†, Qiukui Hao1,3†, Jianghua Zhou3 and Birong Dong1,3*
Abstract Background: Gastric cancer is a major health problem, and frailty and sarcopenia will affect the postoperative outcomes in older people. However, there is still no systematic review to determine the role of frailty and sarcopenia in predicting postoperative outcomes among older patients with gastric cancer who undergo gastrectomy surgery. Methods: We searched Embase, Medline through the Ovid interface and PubMed websites to identify potential studies. All the search strategies were run on August 24, 2016. We searched the Google website for unpublished studies on June 1, 2017. The data related to the endpoints of gastrectomy surgery were extracted. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the association between sarcopenia and adverse postoperative outcomes by using Stata version 11.0. PRISMA guidelines for systematic reviews were followed. Results: After screening 500 records, we identified eight studies, including three prospective cohort studies and five retrospective cohort studies. Only one study described frailty, and the remaining seven studies described sarcopenia. Frailty was statistically significant for predicting hospital mortality (OR 3.96; 95% CI: 1.12–14.09, P = 0.03). Sarcopenia was also associated with postoperative outcomes (pooled OR 3.12; 95% CI: 2.23–4.37). No significant heterogeneity was observed across these pooled studies (Chi2 = 3.10, I2 = 0%, P = 0.685). Conclusion: Sarcopenia and frailty seem to have significant adverse impacts on the occurrence of postoperative outcomes. Well-designed prospective cohort studies focusing on frailty and quality of life with a sufficient sample are needed. Keywords: Gastric cancer, Sarcopenia, Frailty, Postoperative complications
Background Gastric cancer constitutes a major health problem worldwide and is the second most common cause of cancer death [1]. Surgical resection is the main treatment for gastric cancer. Several studies have pointed out that old and young patients carry potential differences in surgery [2, 3]. Older gastric-cancer patients who undergo gastrointestinal surgery may encounter more adverse * Correspondence: [email protected] † Equal contributors 1 The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, #37 Guoxuexiang, Chengdu, Sichuan 610041, China 3 Collaborative Innovation Center of Sichuan for Elderly Care and Health, No. 783, Xindu Lu, Chengdu, Sichuan 610500, China Full list of author information is available at the end of the article
postoperative outcomes than younger patients [4]. Thus, the need exists to assess the risk of gastrointestinal surgery, especially in older gastric cancer patients. The prevalence of frailty increases with aging [5]. Frailty is defined as a clinically recognisable state of older adults with increased vulnerability, resulting from age-associated decline in physiological reserve and function across multiple organ systems [5, 6]. Frailty assessment may be a very useful tool for preoperative risk assessment in gastric cancer patients. By assessing frailty, patients can be assigned to undergo either a more tailored individual approach or a standard treatment [5]. Sarcopenia is a syndrome characterised by progressive and generalised loss of skeletal muscle mass and
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Shen et al. BMC Geriatrics (2017) 17:188
strength [7] and is an important geriatric syndrome closely related to frailty syndrome [8–10]. Increasing evidence shows that frailty or sarcopenia is related to the risk of adverse postoperative outcomes, including morbidity, institutionalisation, prolonged length of hospitalisation, and mortality [2, 9, 11]. Therefore, assessment of frailty and sarcopenia is necessary for older gastric-cancer patients potentially undergoing surgery [5, 12–14]. However, studies concerning the benefit of assessing frailty and sarcopenia in older patients with gastric cancer undergoing gastric surgery are scarce, and the conclusions are inconsistent [2, 9, 11, 15]. Therefore, we conducted this systematic review and meta-analysis aiming to examine the impact of frailty or sarcopenia on postoperative outcomes in older patients undergoing elective gastrectomy surgery.
Methods Search strategy
We searched the following electronic databases: (1) MEDLINE (Ovid, 1946 to August 24, 2016); (2) EMBASE (Ovid, 1974 to August 24, 2016). We used medical subject headings (MeSH) or equivalent and text word terms for MEDLINE and adaptations of the search strategy for EMBASE. We also searched the PubMed web version on August 24, 2016 (https://www.ncbi.nlm.nih.gov/ pubmed/), and Google website (www.google.com) for unpublished studies on June 1, 2017. As mentioned in the methodology specified under the PRISMA guidelines (www.prisma-statement.org), two researchers (YJS and JHZ), in collaboration with a medical librarian, performed a systematic search. The following keywords were used for the search: gastric cancer, aged, frailty, sarcopenia, geriatric assessment, postoperative complications and postoperative outcomes. The search string is included in detail in the Additional file 1. We tailored searches to individual databases. The search was completed on August 24, 2016, and animal restriction was applied. In addition, the reference lists of the selected articles were also reviewed to identify relevant articles. Study selection
Studies were eligible if they reported postoperative outcomes in older patients with gastric cancer in relation to frailty or sarcopenia profile. We included both retrospective and prospective cohort studies, which described clinical trials in which patients, with an average age of 60 years and older, underwent elective gastric surgery for gastric cancer and were categorised into frail or sarcopenic and non-frail or non-sarcopenic groups. In addition, the criteria used to categorise the patients into frail or sarcopenic groups had to be clearly reported, and frailty or sarcopenia had to be determined in a clinical setting. Studies were excluded if they did not examine postoperative
Page 2 of 8
outcomes or surgical complications such as wound infection, anastomotic leakage or mortality as endpoints. The titles and abstracts of the articles were screened by two investigators (YJS and JHZ). Whenever an article was considered relevant, we reviewed the full text. Finally, to identify potentially eligible studies, we also reviewed all the references in lists of the included studies. We resolved disagreements by discussion to reach a consensus with a third review author (BRD). Data charting
One reviewer (YJS) extracted the following data from the included studies: first author, study population, study design, sample size, age of the participants (mean age and standard deviation, if reported), year of publication, country and period of enrolment and inclusion and exclusion criteria of the study. Another reviewer (JHZ) independently double-checked this process. We extracted data regarding the targeted endpoints of this review: criteria and prevalence of frailty and sarcopenia and postoperative outcomes in relation to frailty and sarcopenia groups. If the data in the original manuscript was insufficient, the corresponding author was contacted for additional information. Critical appraisal
Reviewers YJS and JHZ independently assessed the methodological quality of the included studies by the Methodological Index for Non-Randomized Studies (MINORS). For non-comparative studies, this instrument consists of the following eight items: (1) a clearly stated aim, (2) inclusion of consecutive patients, (3) prospective collection of data, (4) endpoints appropriate to the aim of the study, (5) unbiased assessment of the study endpoint, (6) follow-up period appropriate to the aim of the study, (7) loss to follow-up less than 5% and (8) prospective calculation of the study size. If the information is not reported, an item is scored 0 points; if the information is reported but inadequate, it scores 1 point; if the information is reported and adequate, it scores 2 points. The ideal score is 16 for noncomparative studies. During a consensus meeting, disagreement among the reviewers was discussed with a third reviewer (BRD). Statistical analysis
If there was no available data to extract and pool, we described the outcomes in our review. The summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of the included studies were used as measures to assess the association of sarcopenia with postoperative complications. We measured heterogeneity by using the chi2 test with significance set at P < 0.1. The I2 is also computed; it is a quantitative measure of inconsistency
Shen et al. BMC Geriatrics (2017) 17:188
across studies. The following is a rough guide to interpretation of I2: 0% to 30% might not be important; 30% to 60% may represent moderate heterogeneity; 60% to 75% may represent substantial heterogeneity; 75% to 100% represents considerable heterogeneity. Clinically, there is heterogeneity because of the different evaluation methods of sarcopenia and follow-up time. In consideration of the presence of clinical heterogeneity, we used the random-effects model to synthesise all data, regardless of heterogeneity between the pooled studies in statistical order to obtain more conservative results. Publication bias was assessed by visually inspecting the funnel plots and Egger’s and Begg’s tests (P < 0.10). Subgroup analysis was conducted according to different designs of included studies. Sensitivity analysis was performed by omitting each study or included studies with lower quality. The STATA version 11.0 (Stata Corp, College Station, TX, USA) was used to perform all of the analyses. If a P value was 65
Japan
prospective study
7/2012–1/2015
Inclusion - Elective gastric surgery Exclusion - combined resection
ASA grade ≤ III gastric denocarcinoma
255
65.14 (10.81)
China
prospective study
8/2014–3/2015
Inclusion - Elective gastric surgery Exclusion - unresectable
Tegels JJ et al., 2015 [15]
gastric adenocarcinoma
149
69.6 (37–88)
Netherlands retrospective study
1/2005–9/2012
Inclusion - Elective gastric surgery Exclusion - None
Zhuang CL et al., 2016 [24]
gastric cancer
937
64.0 (median15.0)
China
retrospective study
12/2008–4/2013 Inclusion - Elective gastric surgery Exclusion - None
Chen FF et al., 2016 [19]
undergoing TG with 158 D2 lymphadenectomy for gastric cancer
66.9 ± 8.7
China
prospective study
8/2014–2/2016
Nishigori T et al., 2016 [25]
gastric cancer
>60 Japan (average age)
retrospective study
3/2006–10/2014 Inclusion –LTG Exclusion -None
157
Design
Inclusion - histologically proven gastric adenocarcinoma -ASA grade of III or less Exclusion - unresectable
Legend: SD standard deviation, NR not reported. LTG laparoscopic total gastrectomy, ECOG Eastern Cooperative Oncology Group
One study (Tegels, JJ et al.) [20] used GFI ≥3 to define frailty, and the results show a significant relationship between frailty and surgical mortality in gastric cancer (OR 3.96; 95% CI: 1.12 to 14.09, P = 0.03). This study also explored the relationship between frailty and serious adverse events, length of stay, and 6-month mortality. In this study, frailty was associated with increased risk of serious adverse events (defined as Clavien–Dindo grade 3a or over); however, frailty did not correlate with either increased 6-month mortality or increased length of stay. Six studies reported the association between sarcopenia and postoperative complications. We calculated the summary OR values using random-effects models; the pooled OR of gastric cancer from the combination of included studies was 3.12 (95% CI: 2.23–4.37) for
studies were hospitalised patients with a mean age over 60 years old, and the prevalence of sarcopenia ranged from 12.5% [23] to 57.7% [15]. Frailty or sarcopenia and postoperative outcomes
The outcomes reported in all included studies in relation to frailty or sarcopenia were in-hospital mortality [20], postoperative complications [19, 21–25], serious adverse events [20, 22, 24], hospital costs [23], overall survival [24], disease-free survival [24] and surgical site infection [25]. The postoperative complications of the studies were classified into different severity grades by using a well-described classification system (Clavien–Dindo, 2004) [26]. The classification systems used are summarised in Table 4. Table 2 Results of the MINORS quality assessment Study, Author, year
Clearly stated aim
Inclusion of consecutive patients
Consecutive patients Prospective collection of data
Endpoints appropriate to the aim of the study
Unbiased assessment of the study endpoint
Follow-up period appropriate to the aim of the study
Loss to follow-up
